{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T19:38:29Z","timestamp":1766086709312},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T00:00:00Z","timestamp":1331683200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Contrast Media &amp; Molecular"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>The development of magnetic resonance imaging (MRI) contrast agents targeting epitopes in atherosclerosis is of general interest. In particular, early detection of activated platelets as key players in plaque rupture could provide improved triage of patients. However, so far the efficiency of contrast agents targeting human pathologies can only be examined in animal experiments, which do not necessarily reflect human <jats:italic>in vivo<\/jats:italic> conditions. We therefore describe application of a contrast agent targeting activated human platelets in an MRI tissue flow chamber, allowing detection and characterization of contrast agent binding. Microparticles of iron oxide (MPIO) were conjugated to an antibody targeting ligand\u2010induced binding sites (LIBS) on the activated platelet glycoprotein IIb\/IIIa\u2010receptor or to control antibody, resulting in LIBS\u2013MPIO or control\u2013MPIO contrast agent. Human endarterectomy specimens from patients with acute stroke or transient ischemic attack were imaged <jats:italic>ex vivo<\/jats:italic> before and after contrast agent perfusion using a 9.4\u2009T MRI system. Specimens were measured under static (<jats:italic>n\u2009=<\/jats:italic>\u200918) or flow conditions (<jats:italic>n\u2009=<\/jats:italic>\u200918) in a specially designed flow chamber setup, simulating physiological conditions in a stenosed vessel. A significant MPIO\u2010induced negative contrast was achieved in MRI by LIBS\u2013MPIO in specimens under static and flow conditions (LIBS\u2013MPIO vs control\u2013MPIO: <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), and the location of LIBS\u2013MPIO binding corresponded well between histology and MRI (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The number of MPIOs per platelet area on endarterectomy specimens in histology was significantly higher with LIBS\u2013MPIO (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Furthermore, the intensity of contrast agent binding and signal change showed the potential to reflect the severity of clinical symptoms. LIBS\u2013MPIO allows the detection of activated platelets on the surface of symptomatic atherosclerotic human plaques using molecular MRI. Furthermore, the MRI tissue flow chamber setup described could help to evaluate binding properties of contrast agents, and might therefore be an interesting tool for contrast agent development from animal experiments towards clinical application. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cmmi.482","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T13:05:29Z","timestamp":1332248729000},"page":"204-213","source":"Crossref","is-referenced-by-count":9,"title":["An approach towards molecular imaging of activated platelets allows imaging of symptomatic human carotid plaques in a new model of a tissue flow chamber"],"prefix":"10.1002","volume":"7","author":[{"given":"Dominik","family":"von Elverfeldt","sequence":"first","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirko","family":"Mei\u00dfner","sequence":"additional","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlheinz","family":"Peter","sequence":"additional","affiliation":[{"name":"Atherothrombosis and Vascular Biology Baker Heart Research Institute  Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Meixner","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Neudorfer","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Merkle","sequence":"additional","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Harloff","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurophysiology University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Zirlik","sequence":"additional","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Sch\u00f6llhorn","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Markl","sequence":"additional","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Hennig","sequence":"additional","affiliation":[{"name":"Department of Radiology\u2013Medical Physics University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Bode","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin","family":"von zur Muhlen","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology University Medical Center Freiburg  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.02867.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27196"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1548"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.165498"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22385"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1753"},{"issue":"1","key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1053\/j.seminoncol.2010.11.002","article-title":"Molecular magnetic resonance contrast agents for the detection of cancer: past and present","volume":"38","author":"Bogdanov A","year":"2011","journal-title":"Semin Oncol"},{"key":"e_1_2_7_9_1","first-page":"1198","article-title":"A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI","volume":"118","author":"Zur Muhlen C","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.753657"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20342"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20718"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200503-379OC"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000158478.29668.9B"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.058883"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.106.138875"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000232317.84122.0c"},{"issue":"14","key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1096\/fj.04-1513fje","article-title":"Single\u2010chain antibodies for the conformation\u2010specific blockade of activated platelet integrin \u03b1IIb\u03b23 designed by subtractive selection from naive human phage libraries","volume":"18","author":"Schwarz M","year":"2004","journal-title":"FASEB J"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000135660"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000054671.71777.C7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.194.2.7824727"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.11.6.1678"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2010.07.021"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403918101"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043430"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0298"},{"issue":"2","key":"e_1_2_7_27_1","first-page":"59","article-title":"A functionalized magnetic resonance contrast agent selectively binds to glycoprotein IIb\/IIIa on activated human platelets under flow conditions and is detectable at clinically relevant field strengths","volume":"7","author":"Muhlen C","year":"2008","journal-title":"Mol Imag"}],"container-title":["Contrast Media &amp; Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmmi.482","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmmi.482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T09:54:38Z","timestamp":1696931678000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cmmi.482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["10.1002\/cmmi.482"],"URL":"https:\/\/doi.org\/10.1002\/cmmi.482","archive":["Portico"],"relation":{},"ISSN":["1555-4309","1555-4317"],"issn-type":[{"value":"1555-4309","type":"print"},{"value":"1555-4317","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3]]}}}